Differential diagnosis of pituitary enlargement.

Enlargement of the pituitary gland is heterogenous in the etiology. Common causes of pituitary enlargement are physiological hypertrophy during pregnancy, primary and secondary tumors, autoimmune hypophysitis including side effects of anticancer therapy with check-point inhibitors. Terms like hypertrophy, hyperplasia, sellar expansion and hypophysitis are commonly used to describe enlargement of the pituitary gland on MR scan regardless its etiology. The most common pathology causing pituitary gland enlargement is pituitary adenoma. Magnetic resonance imaging can differentiate pituitary tumors from diffuse enlargement due to hypophysitis in most but not all cases. Changes on imaging during time or response to pharmacotherapy might help determine the final diagnosis in uncertain cases. We present a case report of a young woman with sellar expansion due to prolonged untreated peripheral hypothyroidism mimicking pituitary adenoma. Interdisciplinary cooperation of endocrinologist, radiologist and neurosurgeon is crucial in determining the diagnosis.

A Prospective Single-Center Study of the Effects of Repetitive Transcranial Magnetic Stimulation at 2-Week Follow-Up in 17 Patients with Chronic Orofacial Pain Diagnosed by Infrared Thermography.

BACKGROUND Infrared thermography is a diagnostic method used to monitor acute and chronic orofacial pain syndrome. Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation. This prospective study from a single center aimed to investigate the effects of rTMS and used infrared thermography as a confirmatory test of orofacial pain. MATERIAL AND METHODS We used infrared thermography to examine the incidence of inflammatory changes as orofacial pain triggers. During the analysis of rTMS effects on patients with orofacial pain, we compared the decrease in pain and the thermal difference in the study group (n=17) and in the research group (n=13). RESULTS In the control group (n=13), there were no statistically significant changes. Both groups showed a significant decrease in self-reported pain. Numerical pain rating scores were significantly lower after S2 stimulation than after S1/M1 (P=0.0071) or sham (P=0.0187) stimulation. The Brief Pain Inventory scores were also lower 3 to 5 days after S2 stimulation than at the pretreatment baseline (P=0.0127 for the intensity of pain and p=0.0074 for the interference of pain), and after S1/M1 (P=0.001 and P=0.0001) and sham (P=0.0491 and P=0.0359) stimulations. CONCLUSIONS The findings from this study support the role of infrared thermography for the diagnosis of chronic orofacial pain, and showed that on the first and fifth days of rTMS therapy in the study group there was a significant reduction of the thermography findings when compared with the control group without rTMS therapy.

Bilateral cortical stimulation for bilateral refractory atypical trigeminal neuropathic pain: Case report.

BACKGROUND: Atypical trigeminal neuropathic pain (aTNP) is a disabling clinical entity. If conservative treatment fails neuromodulation could be indicated. Motor cortex stimulation (MCS) has emerged as an alternative advanced management of such cases. CASE REPORT: We report a case of a patient with bilateral aTNP effectively treated with bilateral MCS. We describe case history, preoperative planning, surgical technique, follow-up and stimulation settings. The surgical technique and the settings used were both gradually adjusted according to current knowledge. CONCLUSIONS: The bilateral MCS led to substantial pain relief in a patient for whom previous pharmacological management had failed. Initial VAS 10/10 with attacks of acute pain was reduced to median VAS 2/10 (maximum VAS 5/10) without acute attacks since the second electrode parameters were set. The reported results for MCS treatment of TNP in the literature demonstrate good long-term efficacy with low complication rates. Although MCS remains to be an off-label procedure, our case demonstrates that in a well-chosen candidate this option could provide impressive results. Although no clear evidence is currently given, we believe that future studies will elucidate indication criteria, surgical technique and stimulation parameters for MCS so it could be offered in a regular basis to patients with refractory pain.

Olfactory Results of Endoscopic Endonasal Surgery for Pituitary Adenoma: A Prospective Study of 143 Patients.

BACKGROUND: Clinical examination, including pre- and postoperative assessment of olfaction function, should be included in evaluating surgical outcomes in patients with pituitary adenomas. Most of the studies are lacking assessment of olfactory function. METHODS: A prospective study of 143 patients who underwent surgical resection of pituitary adenomas from January 2014 to December 2017 was performed. Data on clinical presentation, pre- and postoperative neurologic, endocrinologic, and ophthalmologic examinations, complications, and follow-up outpatient examinations were recorded. Olfactory function was assessed using the Sniffin' Sticks odor identification test preoperatively, postoperatively (3 months), and 1 year after surgery. RESULTS: Normosmia was present preoperatively in 93.7% of patients, postoperatively in 95.8% of patients, and in 95.1% 1 year postsurgery. Hyposmia was present preoperatively in 4.2% of patients, postoperatively in 2.1% of patients, and in 1.4% 1 year after surgery. Anosmia was present preoperatively in 2.1% of patients, postoperatively in 2.1% of patients, and in 3.5% 1 year after surgery. In patients with preoperative normosmia, postoperative hyposmia and anosmia were present in 1.5% of patients. There were no differences according to age, sex, size, or type of pituitary adenoma. CONCLUSIONS: Assessment of olfactory function should be included in the analysis of pituitary adenoma surgery results. This prospective study showed low risk of olfaction deterioration if an endoscopic endonasal approach is used without any mucosal flaps for skull base reconstruction. Further studies that include objective olfaction assessment are warranted.

Olfactory function in patients after transsphenoidal surgery for pituitary adenomas-a short review.

Olfaction is an important sensory input that obviously affects many daily activities. However, olfactory dysfunction (hyposmia and anosmia) leads to a pronounced decrease in quality of life. Surprisingly, little attention has been paid to olfactory changes after transsphenoidal surgery for pituitary tumors. In this review, we summarize current knowledge of the effects of transsphenoidal pituitary surgery on olfaction and compare different surgical techniques. Based on selected studies, the endoscopic approach, in comparison with the microscopic approach, seems to be superior in terms of preservation of olfactory function, although the quality of data from these studies is generally poor. The best results were observed when the endoscopic approach was used without harvesting of the nasoseptal flap.

Treatment of Multifocal Multisystem BRAF Positive Langerhans Cell Histiocytosis with Cladribine, Surgery and Allogenic Stem Cell Transplantation.

Langerhans cell histiocytosis (LCH) is a very rare disease in adults and as well a very rare cause of sellar expansion. The clinical presentation can be heterogeneous, from a single bone lesion to potentially fatal, widespread disease. We describe the difficulties with the diagnosis and treatment of LCH as well as successful treatment with cladribine chemotherapy and allogeneic stem cell transplantation.

Magnetic resonance imaging and histology correlation in Cushing's disease.

INTRODUCTION: We continuously look for new techniques to improve the radicality of resection and to eliminate the negative effects of surgery. One of the methods that has been implemented in the perioperative management of Cushing's disease was the combination of three magnetic resonance imaging (MRI) sequences: SE, SPGR and fSPGR. MATERIAL AND METHODS: We enrolled 41 patients (11 males, 30 females) diagnosed with Cushing's disease. A 3D tumour model with a navigation console was developed using each SPGR, fSPGR and SE sequence. The largest model was then used. In all cases, a standard four-handed, bi-nostril endoscopic endonasal technique was used. Endocrinological follow-up evaluation using morning cortisol sampling was performed for 6-34 months in our study. RESULTS: In total, 36 patients (88%) were disease-free following surgery. Our results indicate we achieved 100% sensitivity of MR. Overall, the conformity of at least one donor site, as compared with the places designated on MR, was in 78% of patients. We searched the place of compliance in individual locations. There is a consensus in individual locations in 63 of the 123 cases (or 56%). The correlation gamma function at a 5% significance level was then 0.27. DISCUSSION: The combination of MR sequences (SE, SPGR, fSPGR), neuronavigation system and iMRI led to increased sensitivity of up to 100%. Specificity reached 56% in our study. CONCLUSION: We found a high success rate in surgical procedure in terms of the correlation between MR findings and histology, which leads to remission of Cushing's disease.

The role of early cortisol level in the assessment of the radicality of resection in central Cushing's disease.

INTRODUCTION: To increase radicality and avoid surgical complications new treatment options are under investigation. One of the promising possibilities is to assess early morning cortisol levels on the first and second postoperative day. MATERIAL AND METHODS: We enrolled 34 patients (9 males, 25 females) diagnosed with Cushing's disease. Blood samples to determine cortisol level were taken always at 06:00 and sent to the lab. The samples were taken on the first and second postoperative day. For all patients, standard four-handed, a bi-nostril endoscopic endonasal technique was used. Endocrinological follow-up (6-34 months) was performed using morning cortisol sampling. RESULTS: In total, 36 patients (88%) were disease-free post-surgery. In the group with early postoperative levels of morning cortisol of less than 463 nmol/L, only 2 of 29 patients (7%) exceeded the final morning level of cortisol at follow-up. In patients with early postoperative cortisol levels between 17 nmol/l and 234 nmol/l all subjects showed normal postoperative cortisol levels. DISCUSSION: In 30 of 34 patients (88%), the level of cortisol was within normal limits. The prediction importance of early measurement of cortisol is 93% for patients with early postoperative cortisol levels of less than 463 nmol/L. The prediction importance of early measurement of cortisol is 100% for patients with early postoperative cortisol levels from 17 to 234 nmol/L. CONCLUSION: The monitoring of early morning cortisol levels seems to be an important tool in the management of central Cushing's disease.

Flexible endoscope-assisted evacuation of chronic subdural hematomas.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurosurgical condition with an increasing incidence. Standard treatment of CSDHs is surgical evacuation. The objective of this study is to present a modification of standard burr-hole hematoma evacuation using a flexible endoscope and to assess the advantages and risks. METHODS: Prospectively, 34 consecutive patients diagnosed with CSDH were included in the study. Epidemiological, clinical and radiographical data were collected and reviewed. All patients underwent a burr-hole evacuation of CSDH. A flexible endoscope was inserted and subdural space inspected during surgery. The surgeon was looking specifically for the presence of septations, draining catheter position and acute bleeding. RESULTS: Thirty-four patients underwent 37 endoscope-assisted surgeries. Presenting symptoms were hemiparesis (79%), decreased level of consciousness (18%), gait disturbances (15%), headache (12%), aphasia (6%), cognitive disturbances (6%) and epileptic seizure (3%). Average operative time was 43 min, and the average increase in operative time due to the use of the endoscope was 6 min. Recurrence rate was 8.8%, and clinical outcome was favorable (defined as mRS ≤ 2) in 97% of the cases. CONCLUSIONS: To our knowledge, the present cohort of 34 patients is the largest group of patients with CSDH treated using an endoscope. This technique allows decent visualization of the hematoma cavity while retaining the advantages of a minimally invasive approach under a local anesthesia. The main advantages are correct positioning of the catheter under visual control, identification of septations and early detection of cortex or vessel injury during surgery.

Intraoperative Magnetic Resonance Imaging During Endoscopic Transsphenoidal Surgery of Growth Hormone-Secreting Pituitary Adenomas.

BACKGROUND: The effect of intraoperative magnetic resonance imaging (iMRI) on the extent of sellar region tumors treated endonasally has been described in previous research. However, the effects of iMRI on endocrinologic outcome of growth hormone-secreting adenomas have been studied in only a few small cohort studies. METHODS: Inclusion criteria were primary transsphenoidal surgery for growth hormone-secreting adenoma from January 2009 to December 2014, a minimum follow-up of 1 year, complete endocrinologic data, at least 1 iMRI, and at least 2 postoperative magnetic resonance images. The cohort consisted of 105 patients (54 females, 51 males) with a mean age of 48.3 years (range, 7-77 years). There were 16 microadenomas and 89 macroadenomas. RESULTS: Endocrinologic remission in the whole cohort was achieved in 64 of the patients (60.9%). Resection after iMRI was attempted in 22 of the cases (20.9%). Resection after iMRI led to hormonal remission in 9 cases (8.6%). Endocrinologic postoperative deficit was observed in 10 cases (12.5%). Postoperative cerebrospinal fluid leakage indicated the necessity to reoperate in 3 cases (3.8%). No neurologic deterioration was observed. CONCLUSIONS: iMRI influences not only the morphologic extent of pituitary adenomas resection but also the endocrinologic results. We encourage the routine application of iMRI in pituitary adenoma surgery, including hormone-secreting pituitary tumors.

Expression profiles of somatostatin, dopamine, and estrogen receptors in pituitary adenomas determined by means of synthetic multilocus calibrators.

AIMS: Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA. METHODS: Adenoma specimens were obtained from 206 patients during transsphenoidal resection. For quantitative analysis, reverse transcription and consequent real-time PCR with synthetic multilocus calibrators (SMC) were used. The obtained data were normalized to the number of transcripts of the beta-glucuronidase gene. RESULTS: The use of SMC enabled the alignment of individual calibration functions for all the receptors. No relationships between the expression of the receptors and the tumor size, site of extension, gender or age at diagnosis were significant. In growth hormone-secreting adenomas, D2R and SSTR2 transcripts were extensively expressed, followed by ER1, SSTR5, SSTR3, and SSTR1. In patients with macroprolactinomas, transsphenoidal resection was indicated because dopamine agonists did not normalize prolactin levels. D2R, ER1 and SSTR1 transcripts were significantly transcribed. Corticotroph adenomas showed high levels of D2R and ER1 transcripts and lower amounts of SSTR2 and SSTR1 transcripts. SSTR5 transcripts were very low. Subjects with CNFA dominantly expressed D2R and ER1, followed by SSTR2 and SSTR3 mRNA. CONCLUSION: We evaluated SSTR1-SSTR5, D2R, and ER1 expressions in a large group of pituitary adenomas and we found that determining their individual expression profiles could help when choosing the optimal postoperative treatment.

Endonasal endoscopic pituitary adenoma resection: preservation of neurohypophyseal function.

OBJECTIVES: In the past 10 years, endoscopic resection of pituitary adenomas has become an alternative to microsurgical resection with the additional advantage of increasing the patient's postoperative comfort. This analysis explored whether endoscopic resection can reduce the risk of postoperative neurohypophyseal dysfunction. DESIGN: We rated and compared the need to administer desmopressin during the first four postoperative days and with the need after a follow-up of at least 3 months (chronic administration). SETTING: Three groups of patients were compared: Patients in group 1 were operated on microscopically. Patients in group 2 were operated on endoscopically. Patients in group 3 were operated on endoscopically with intraoperative magnetic resonance imaging (iMRI). PARTICIPANTS: Group 1 was made up of 50 patients treated in 1999; group 2 comprised 50 patients operated on from 2006 to 2007; and Group 3 comprised 50 patients operated on in 2008. MAIN OUTCOME MEASURES: In group 1 the need to use desmopressin postoperatively occurred in eight patients; three needed chronic treatment. In group 2 the need for postoperative application of desmopressin occurred in four patients; none required chronic treatment. In group 3 desmopressin had to be administered postoperatively in five patients but only temporarily. RESULTS AND CONCLUSIONS: Endoscopic surgery is a safe and effective method for the resection of pituitary adenomas. The rate of chronic desmopressin application was reduced. In conjunction with iMRI and navigation, the endoscopic technique allows increased radicality together with fewer adverse effects.

Endoscopic endonasal resection of medial orbital lesions with intraoperative MRI.

BACKGROUND: Various approaches have been described and used for operating on lesions in the orbit. The approach selection is based on the pathology in the orbit and its exact location. This study was performed to evaluate the endoscopic endonasal approach (EEA) for orbital lesions and application of intraoperative MRI (iMRI). METHODS: Since 2006, the present authors have performed 614 endoscopic endonasal procedures. iMRI was used in 409 of these cases. Three orbital lesions approached via the endonasal route with a minimum follow-up of 1 year were analysed. RESULTS: EEA was used in one case of intraconal cavernoma, one extraconal cavernoma and one solitary fibrous tumour in the orbit. The lesion was located medially to the optic nerve in all cases. Radical resection was achieved and the patient's vision was improved in two cases with a preoperative visual field deficit. iMRI was useful in two cases. In one case intraoperative MRI helped to find an intraconal lesion; in the other case iMRI led to evacuation of haemostatic material and blood, which was causing compression in the orbit. CONCLUSIONS: The EEA should be considered whenever a lesion in the orbit is located medially to the optic nerve. Excellent results were achieved. iMRI proved useful in selected cases.

Dopamine 2 receptor expression in various pathological types of clinically non-functioning pituitary adenomas.

Clinically non-functioning pituitary adenomas account for about one-third of pituitary tumors. The majority of them are pathologically classified as gonadotropinomas or null-cell adenomas without hormonal expression. The rest represent silent corticotroph adenomas and plurihormonal tumors. Conservative therapy with dopamine agonists is effective in some cases only depending on the expression of dopamine 2 receptors (D2R). The aim of this study was to quantitatively estimate D2R expression in clinically non-functioning pituitary adenomas and correlate the results with adenoma type according to pathological classification. Out of the 87 adenomas investigated, 63 expressed gonadotropins, 7 were silent corticotroph adenomas, 7 were plurihormonal tumors, and only 6 did not express any pituitary hormone on immunohistochemical investigation. With the use of the reverse transcriptase PCR technique, D2R mRNA was expressed in all adenomas with very heterogeneous quantity. The expression was very low in corticotroph adenomas (relative median quantity after normalization to housekeeping gene 0.01) and lower in plurihormonal tumors (median 0.4) than in gonadotroph (median 1.3) and null-cell adenomas (median 1.9). The difference between corticotroph adenomas and plurihormonal tumors in comparison with other pathological types was statistically significant. The expression of D2R did not depend on the presence or absence of gonadotropins. We conclude that D2R expression is very low in corticotroph adenomas and significantly lower in plurihormonal tumors. The positivity of gonadotropins does not predict the D2R quantity.

One year experience with 3.0 T intraoperative MRI in pituitary surgery.

A multifunctional surgical suite with intraoperative 3.0 T MRI (ioMRI) has been operating at the Central Military Hospital, Prague since April 2008. Our experiences over the past year and the effect of ioMRI on the extent of pituitary adenoma resection are evaluated. Eighty-six pituitary adenoma resections were performed in 85 patients with ioMRI in the first year of the ioMRI service. Pituitary adenoma suprasellar extension was present in 60 cases, invasion into cavernous sinus in 49 cases, and retrosellar growth in one case. The surgical goal was set before surgery: either a radical resection (49 cases) or a partial resection (37 cases). In the group of patients where a decision for a radical resection was taken the results are as follows: ioMRI confirmed radical resection in 69.4% of the cases; ioMRI disclosed unexpected adenoma residuum and further resection led to radical resection in 22.4%. In the group of patients where a decision for a partial resection was taken, the results are as follows: no further resection was perfomed after ioMRI in 51.3% of the cases and further resection was performed after ioMRI in 48.7% of the cases. ioMRI seems to be a valuable tool to increase the extent of pituitary adenoma resection.

Postoperative epidural fibrosis.

BACKGROUND: Epidural fibrosis (EF) is defined as nonphysiologic scar formation, usually at the site of neurosurgical access into the spinal canal, in intimate vicinity to and around the origin of the radicular sheath. From the very onset, EF behaves as a reparative inflammation causing, as a rule, clinical problems of characteristic nature and dynamism (pain). Treatment for EF, the role and mode of application of corticosteroids for EF management are, to this day, a moot point in algesiologic literature. The authors conducted a prospective study designed to obtain new data for assessing the anti-inflammatory effects of corticosteroids with special regard to the part played by steroids in the development of EF. The study also aimed at rating EF in terms of its effects on the intensity and character of the patient's symptoms after surgery for herniated intervertebral disc in the lumbar region. METHOD: A double-blind prospective study was conducted to investigate a cohort of 200 patients requiring surgical treatment for intervertebral disc hernia (hernia disci intervertebralis). The patients were randomly and blindly divided into 2 groups, one on peroperatively applied local doses of a mix containing corticosteroids, the other without such medication. All the requirements of a double-blind study, including statistical assessment of the results, were observed throughout the diagnostic and therapeutical processes. The results were processed relative to the: clinical finding, subjective intensity of symptoms rated on a visual analog scale, radiographic finding (magnetic resonance imaging: plain and after contrast medium application). RESULTS: A statistical comparison of the clinical picture in the 2 surgically treated groups failed to reach statistical significance. Nevertheless, a trend toward better clinical picture in the steroid mix group was observed. Paradoxically, when statistically compared, the rate of EF build-up was found greater in the steroid-treated group. A 5% statistical significance was established in the correlation between the presence of EF and the patients' subjective rating (difference between input and output visual analog scale).

The epidural steroids in the prevention of epidural fibrosis: MRI and clinical findings.

BACKGROUND: Epidural fibrosis (EF) represents a frequent and poorly manageable complication of lumbar disk surgery. OBJECTIVES: To investigate the influence of perioperative Epidural Steroid (ES) application on the development of EF. METHODS: One hundred and seventy eight patients underwent L4/5 or L5/S1 discectomy. The study group receiving ES comprised of eighty five patients, and a further control group comprising eighty two patients received a placebo. At a 12 month follow-up, all subjects underwent contrast magnet resonance imaging of the lumbosacral spine. One hundred and sixty seven patients filled in a predetermined questionnaire containing the Visual Analogue Scale (VAS; pain scale) during the first postoperative days and 12 months after. Intergroup differences were analysed and a correlation between the extent of EF and VAS was examined. RESULTS: The groups did not differ regarding the extent of EF. There was a statistically significant correlation between the degree of fibrosis and VAS (P<0.05). However, there was no significant difference in subjective pain assessment between both groups 12 months postoperatively. The application of ES did not influence their return to work. Patients receiving ES experienced less pain on the first and third days after surgery. The average hospital stay after surgery was shorter in the steroid treated group (4.5 days) compared to 5.2 days in the control group (p<0.05). CONCLUSIONS: The application of ES did not prove to be useful in the prevention of Failed Back Surgery Syndrome and epidural scar formation. Postoperative pain was decreased in the steroid treated group during the first postoperative week, but not 12 months postoperatively.